Antitubercular serum and method of producing the same



Patented July 10, 1928.

UNITED STATES 1,676,997 PATENT OFFICE.

i CONSTANTINE LEVENTIS, OF PHOENIX, ARIZONA.

ANTITUBEBCULAR SERUM AND' METHOD OI PRODUCING THE SAME. i

No Drawing.

offensive action of the infectious germs after manifestation of' the disease, and thus producing cure.

In the heretofore customary manner of producing antitoxins and antibacterial serums for medical use, animals are injected with specific toxins, antigens or specific infectious germs in such a manner that the blood of the animal graduallybuilds up a resistance to the specific toxin or infectious germ with which it has been injected. After a sufficient number of suitable injections the blood of the animal becomes. so resistant that the animal becomes immune to that specific toxin or infectious germ. When the animals are thoroughly immunized they are bled and their serum is taken for medical use. A great variety of antitoxins and antibacterial serums are made in substantially the above described manner such, for instance, as-diphtherla antltoxin, antlpneum '35 ococcus serum and the like.

Studying in general the serotherapy against all infectious diseases and observing the results obtained with serotherapy, I came to the conclusion that antitoxins and anti- 40 bacterial serums do not destroy the infectious germs in the body organism but disintoxicate the body organism of their toxins and protect thebody organism against the further offensive action of the infectious germsbysupplying the body organism with protective substances.

is often unable to produce these protective substances by itself and check thus the further rapid multiplication of the infectious germs.

In considering why it has heretofore been possible to accomplish protection of the body organism, by means of antitoxins and anti bacterial serums, against some infectiousgerms and impossible to accomplish that protection against other infectious germs The body organism- Applicatlon filed-April 28, 1928. Serial No. 273,778&

notably pneumococci of all four types and tuberculosis, I came to the following con clusi'on:

The body organisms of the different animals, including the human organism, react in a different way when infected by the same infectious germs. The common, tendency is to form within the organism, and usually in the blood, protective substances against the infectious germs. Many organisms perform thatprotection easily, while others cannot succeed to protect themselves. The

same infectious germs when introduced into different body organisms act in differentmanners to increase and multiply. They become more virulent or attenuated according to the body organism, culture medium, in which they find themselves. Thus, in order that two different body organisms, infected with the same specific germs should produce the same protective substances they must first somehow become similar as culture media for the infectious germs. Then, under these conditions, antitoxins or antibacterial serums, from either of the two different body organisms, will act as protective substances when applied to the other of the two species of different body organisms which has been selected.

As an illustration of this, if we wishto protect a rabbit, against the infection of a specific germ, with serum taken from a goat immunized with the same specific germ, we must first link together the body organisms of both animals. That is, we must inject the body organism of the immunized goat with serum taken from-the rabbit. Then,

the body orga'nismof'the goat'will not only provide protective substances, effective against the infectious germ, in relation to goats, as a class, but the goat body organism will, at the same time, provide substances effective against the infectious germ in relation to rabbits, as a class. With serum thus produced, the rabbit may be protected against the infection of a specific germ with serum taken from the goat. I

I have discovered that, in a similar manner, antitoxins and antibacterial serums may be made from the blood of the lower animals which are effective to protect the human organism against' the infection of specific germs. This is efiected by suitably 1njecting the immunized or antigen treated lower, animal with human serum and then preparing the antitoxin substance or, antirotective i lltl with human serum, a prpcess which prior to reaches five billions, avoidi the present invention h s never been used. A serum may thus \bejproduced which will be effective to protect the human organism against tuberculosis.

Prior to my invention attempts were made ti) prepare antibacterial serum against tuberculosis but without any success, In order that the invention ma. be better understood the following 'speci example of the preparation of serum is given Preparation of antz'tuberoulosis serum.

The animals, preferably donkeys, are previously tested with tuberculin and mallem. The first injections are with very attenuated killed tubercle bacilli in "suspension and are made subcutaneously. The first doses are small, in the neighborhood of 100,000,000 of the ,very attenuated or killed'bacilli. Progressively' the dose is increased until it g in this way any severe reaction. i

Then starting with of the former dose, or substantially 50,000,000 of the very attenuated or killed tgplercle bacilli, intravenous injections are ade. This ClOSBdS progressively increased in subsequent 1nections until the dose" increased to five illions. The animal is iilen injected intravenously with one billio' of the Very attenuated or dead tubercle bacilli in suspen:

sion together with ccQof human serum.

This brings on a very evere reaction, lasting frequently for a week. In this reaction the animal shivers with high temperature of.

from 102 to 104 degrees.

The-animals are allowedvto rest for days and then subcutaneously injected with ,one cc. of sputum of a tubercular patient suffering from a very active. tuberculosis. The sputum must show at least tubercle bacilli in each field. In the place of the injection of the sputum there is formed an abscess'; with a large area .of inflammation.

The animal becomes sickv with temperature and loss of appetite. This condition continues for a week or twelve days, when the abscess is broken and inflammation and tem perature subside. months for the tubercular abscess to heal completelygand for the animal to increase in weight.

The animal is then allowed to rest for another month to recover completely from the infection. Ten to twenty cc. of human serumare then injected intravenously which produces severe reaction with symptoms of anaphylaxia. The seventh day after the in- It takes two to three serum as herein described requires a period of at least eight to ten months.

The therapeutic dose in adults isten drops injected subcutaneously and is repeated at intervals of seven days until a total of three injections have been made. After an interval of twenty days two or three more injections are made, again at intervals of seven days. The number of these second injections is governed according to the slight local reaction, which consists in redness and itching. The administration of the doses is accomplished without .any systematic disturbance ofthe organism and without disturbing the welfare of the atient. After the two preliminary series 0 injections, the injections are continued, as above at intervals of two months until satisfactory results are obtained.

While I have described certain methods 7 by which humanized serums maybe made, I do'not WlSh to confine myself to these spe ClfiC methods, nor do I wish to confine m self to the preparation of the specific su stances named. The methods may be varied or changed in any way which may seem 8dvisable to suit existing conditions, without departing from the spirit of'the invention. While I have described methods in which dead, attenuated or living bacteria were used, I do not wish to thus confine myself, but,ma.y instead, make use of toxins giveh off by the living bacteria or liquid extracts from cultures, disintegrated micro-organ- .isms or disintegrated products of the bacterial cells or even certain micro-organisms or their products which arenot associated in any way with the production of the specific affection.

I claim:

antitoxins and .serums, treating an animal with tubercular antigen, injecting serum from an animal to be protected and of a different species into said treated animal and withdrawing the serum from the treated animal.

2. In the process of preparing tubercular .antitoxins and serums for specific animal use, injecting an animal of a species other than the specific animal with tuberculosis. toxin or bacterial extract, injecting the 1. In the process of preparing tubercular ing an animal with a tuberculosis antigen,

injecting human serum into the said treated animal and withdrawing serum from the thus treated animal.

4. In the process of preparing tuberculosis antitoxins and serums, treating .an animal not normally responsive to tuberculosis with tuberculosis antigen, injecting into the said treated animal serum from an animal nornu'tlly responsive to tuberculosis thereby making the said treated animal responsive to tuberculosis, and withdrawing serum from the thus treated animal.

5. An anti-tubercular serum derived from the blood of an animal whieh is not nor mally responsive to tuberculosis, but which has been made responsive by injection with tuberculosis antigen and serum of a responsive animal.

ture.

CONSTANTINE LEVENTIS,'M. D.

In testimony whereof I atlix my signa- 

